This renewal contains the research projects of six investigators, plus an outreach clinical program. All of six projects investigate clinically relevant problems taking cellular and molecular biological approaches to solve them, on either human or experimental material. Two projects (Drs. Unanue and Loh) use murine experimental systems while the remaining four (Drs. Parker, Schwartz, Chaplin and Lublin) deal directly with human material. The blending of basic scientists and clinical investigators in this program should create a mutally beneficial situation. The project of Dr. Emil R. Unanue deals with cellular immunity to infection and the regulation of antigen presentation using an experimental model of a mouse mutant strain that lacks lymphocytes. Dr. Dennis Loh uses molecular biological approaches with transgenic mice to study T cell recognition and autoimmunity. Dr. Charles Parker tackles the molecular genetics of the allergic state. He and his associates examine for the distribution and possible genetic polymorphism of severaal genes claimed to be associated with allergies, plus examine the human IL-4 protein. Dr. Benjamin Schwartz uses cells transfected with HLA DR genes to study the recognition of influenza virus. He wants to examine how the class II histocompatibility molecules function in binding flu peptides, an issue relevant for our understanding of the anti-viral T cell response. Dr. David Chaplin examines the molecular genetics of systemic lupus erythematosus. His use of molecular biological technology may help us in understanding the genetic susceptibility of this frequent autoimmune disease. Dr. Douglas Lublin uses molecular biological approaches to study the decay accelerating factor of complement. His main interest is to study how the complement system is regulated during immune inflammation. All the projects, therefore, employ current molecular and cellular technologies to try to get to a basic understanding of the normal and abnormal immune response. Finally, Dr. James Wedner proposes an outreach program that will deal with the effect of an educational program on the long term clinical response of asthmatics.